Polymorphisms of SOCS-1 are associated with rapid HIV progression rate.

Hersberger, Martin; Schlaepfer, Erika; Buehler, Marco; Bochud, Pierre-Yves; Vernazza, Pietro; Marti-Jaun, Jacqueline; Nemeth, Johannes; Zwahlen, Marcel; Schmidlin, Kurt; Speck, Roberto F (2020). Polymorphisms of SOCS-1 are associated with rapid HIV progression rate. Journal of acquired immune deficiency syndromes JAIDS, 84(2), pp. 189-195. Lippincott Williams & Wilkins 10.1097/QAI.0000000000002319

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OBJECTIVES Immune activation, among other driven by IFN-α and -γ activation is a main feature of progressive HIV infection. Suppressor of cytokine signaling (SOCS) 1 and 3 are negative feedback regulators of the IFN-α and -γ axis. Here, we analyzed the role of 9 single nucleotide polymorphisms (SNPs) within SOCS-1 and 3 genes for their association with HIV progression rate in a cohort of 318 rapid vs 376 slow progressors from the Swiss HIV Cohort Study. DESIGN AND METHODS: We analyzed 9 SNPs, which we have identified in Swiss blood donors, in a cohort of HIV-infected patients (n=1144), which have been categorized according to the decline in CD4+ T-cell counts. In all the conducted analyses, we focused on the comparison between rapid and slow progressors with regard to SNPs in SOCS1 and -3 and with regards to haplotypes using multivariate logistic regression models. RESULTS Three SOCS-1 SNPs (rs193779; rs33989964; and rs4780355) are associated with a risk reduction for rapid progression. Two of these SNPs, rs33989964 and rs4780355, are in strong linkage disequilibrium forming a frequent haplotype. Homozygous carriers of this haplotype are also associated with a risk reduction for rapid progression. In contrast, the minor TT genotype of rs33977706 is associated with twice the risk for rapid progression. No associations have been observed for the four SOCS-3 SNPs or the major SOCS-3 haplotypes. CONCLUSION Our data suggest that SNPS in SOCS-1 are associated with HIV disease progression and speak in favor that immune activation is causal for the progressive immunodeficiency.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

UniBE Contributor:

Zwahlen, Marcel and Schmidlin, Kurt

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0894-9255

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Andrea Flükiger-Flückiger

Date Deposited:

13 Mar 2020 17:19

Last Modified:

26 May 2020 19:44

Publisher DOI:

10.1097/QAI.0000000000002319

PubMed ID:

32097250

BORIS DOI:

10.7892/boris.141272

URI:

https://boris.unibe.ch/id/eprint/141272

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